Managing dysphonia in paediatric patients with complex airway conditions.

OBJECTIVE: To suggest a phonosurgical management strategy that can be used for children who have previously undergone laryngotracheal reconstruction. METHODS: This cases series describes three children who presented with complex, multi-level airway stenosis and marked dysphonia. Phonosurgical intervention involved endoscopic and open approaches, and was combined with voice therapy. A phonosurgical reconstruction management algorithm is suggested for evaluating and treating these complex conditions. RESULTS: Pre-operative assessment is critical, and should involve voice analysis and glottal anatomy assessment using office laryngoscopy and stroboscopy. The risks must be weighed up against the benefit of vocal improvement. Surgical intervention should involve combined endoscopic and open approaches. CONCLUSION: Voice restoration after paediatric airway reconstruction is a complex challenge. Surgical intervention should be conducted in a step-by-step manner to reduce the risk of worsening dysphonia and airway compromise. The risks and benefits must be carefully explored and discussed.

Behavior of poly(glycerol sebacate) plugs in chronic tympanic membrane perforations.

The tympanic membrane (TM), separating the external and middle ear, consists of fibrous connective tissue sandwiched between epithelial layers. To treat chronic ear infections, tympanostomy drainage tubes are placed in surgically created holes in TMs which can become chronic perforations upon extrusion. Perforations are repaired using a variety of techniques, but are limited by morbidity, unsatisfactory closure rates, or minimal regeneration of the connective tissue. A more effective, minimally-invasive therapy is necessary to enhance the perforation closure rate. Current research utilizing decellularized or alignate materials moderately enhance closure but the native TM architecture is not restored. Poly(glycerol sebacate) (PGS) is a biocompatible elastomer which supports cell migration and enzymatically degrades in contact with vascularized tissue. PGS spool-shaped plugs were manufactured using a novel process. Using minimally invasive procedures, these elastomeric plugs were inserted into chronic chinchilla TM perforations. As previously reported, effective perforation closure occurred as both flange surfaces were covered by confluent cell layers; >90% of perforations were closed at 6-week postimplantation. This unique in vivo environment has little vascularized tissue. Consequently, PGS degradation was minimal over 16-week implantation, hindering regeneration of the TM fibrous connective tissue. PGS degradation must be enhanced to promote complete TM regeneration.

Preliminary evaluation of noninvasive microscopic imaging techniques for the study of vocal fold development.

Understanding pediatric voice development and laryngeal pathology is predicated on a detailed knowledge of the microanatomy of the layered structure of the vocal fold. Our current knowledge of this microanatomy and its temporal evolution is limited by the lack of pediatric specimen availability. By providing the capability to image pediatric vocal folds in vivo, a noninvasive microscopy technique could greatly expand the existing database of pediatric laryngeal microanatomy and could furthermore make longitudinal studies possible. A variety of natural-contrast optical imaging technologies, including optical frequency domain imaging (OFDI), full-field optical coherence microscopy (FF-OCM), and spectrally encoded confocal microscopy (SECM) have been recently developed for noninvasive diagnosis in adult patients. In this paper, we demonstrate the potential of these three techniques for laryngeal investigation by obtaining images of excised porcine vocal fold samples. In our study, OFDI allowed visualization of the vocal fold architecture deep within the tissue, from the superficial mucosa to the vocalis muscle. The micron-level resolution of SECM allowed investigation of cells and extracellular matrix fibrils from the superficial mucosa to the intermediate layer of the lamina propria (LP) (350 microm penetration depth). The large field of view (up to 700 microm), penetration depth (up to 500 microm), and resolution (2x2x1microm [XxYxZ]) of FF-OCM enabled comprehensive three-dimensional evaluation of the layered structure of the LP. Our results suggest that these techniques provide important and complementary cellular and structural information, which may be useful for investigating pediatric vocal fold maturation in vivo.

Endoscopic access to the infratemporal fossa and skull base: a cadaveric study.

OBJECTIVES: To demonstrate that the regions of the infratemporal fossa and skull base at the level of the foramen ovale can be visualized endoscopically and that structures can be manipulated within these regions using endoscopic instruments. METHODS: Cadaveric dissection of 3 human cadavers using an endoscopic optical dissector. In all, 6 endoscopic infratemporal fossa and skull base approaches were performed. SETTING: Human temporal bone laboratory. RESULTS: A Gillies incision was coupled with a lateral brow incision, and then subperiosteal planes were developed. Endoscopic visualization and instrumentation was then performed. The infratemporal fossa was readily identified. The skull base at the level of the foramen ovale and the branches of the third division of the trigeminal nerve were seen distinctly. A probe was placed with ease within the foramen ovale itself. CONCLUSIONS: Endoscopic access to the infratemporal fossa is readily accomplished, with excellent visualization and instrumentation ability. This novel technique provides access to this remote region for evaluation, possible biopsy, and potential treatment of infratemporal fossa lesions.

Topical mitomycin application after laryngotracheal reconstruction: a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To explore the effect of mitomycin treatment on the pediatric airway following laryngotracheal reconstruction. DESIGN: Randomized, double-blind, placebo-controlled trial. PATIENTS: Children aged 2 to 17 years with subglottic or upper tracheal stenosis undergoing laryngotracheal reconstruction at a single, tertiary care, children's hospital. INTERVENTION: At the time of extubation or stent removal, the children underwent bronchoscopy and 0.4 mg/mL (2 mL of a 0.2-mg/mL solution of either mitomycin or an equal volume of isotonic sodium chloride was directly applied to the subglottic region for a single application of 2 minutes. These children then underwent interval endoscopy at 2 weeks, 6 weeks, and 3 months postoperatively for assessment of their airways. RESULTS: Granulation tissue was graded on a scale of 0 (none) to 4 (near-total or total occlusion). Videotapes of endoscopies were independently observed and graded by 3 pediatric otolaryngology fellows with a subsequent interobserver agreement of 91.6%. The results were then dichotomized to represent a single cohort in which further surgical intervention would be required and another separate cohort in which further surgery would not be required. At the 1-year mark, interim analysis was performed by a Data Safety and Monitoring Committee. At this time, 13 children had been randomized to the mitomycin-treated arm of the study and 11 children to the placebo-treated arm. A 2-tailed Fisher exact test revealed a value of 1.00. The Data Monitoring and Safety Committee advised that the trial should be stopped because the distributions between the 2 populations were almost identical. CONCLUSION: We cannot reject the null hypothesis that a single topical dose of mitomycin exerts an equal benefit as does isotonic sodium chloride when applied to the pediatric airway after laryngotracheal reconstruction.

Functional magnetic resonance imaging of the pediatric swallow: imaging the cortex and the brainstem.

OBJECTIVE: To design and implement a functional magnetic resonance imaging (fMRI) protocol to investigate the cortical and brainstem patterns of activity in children with regard to the act of swallowing. STUDY DESIGN: Pilot study to assess the clinical feasibility of the project. METHODS: Using a 3T Bruker Biospec 30/60 MRI scanner, images were obtained using the Behavior Interleaved Gradient/Blood Oxygen Level Dependent (BIG-BOLD) image acquisition method. Initially, regions of interest (ROI) were developed to identify the mean time from the onset of a swallow to maximum cortical blood flow in the motor cortex. Using this data to design the BIG-BOLD acquisition method followed by postprocessing of the data, images from two volunteer adults and four volunteer children were obtained. RESULTS: The average time from the onset of a swallow to maximum cortical blood flow was 6 to 8 seconds. Regions of cortical activity include pre- and post-central gyrus (Brodmann's areas 3 and 4), superior motor cortex (B.A. 24), insula, inferior frontal cortex (B.A. 44 and 45), Heschl gyrus (B.A. 41 and 42), putamen, globus pallidus, and the superior temporal gyrus (B.A. 38). Of particular note is the first mapping of the functional activity of swallowing at the level of the brainstem; activity was seen in the region of the nucleus ambiguous. CONCLUSIONS: fMRI provides a novel means of studying the central processes of both normal swallowing and its various pathologic forms in children. Further understanding of how a child coordinates a swallow and how this coordination can be altered at the level of the brainstem and cortex may aid in the development of novel rehabilitative strategies.

Duration of stenting in single-stage laryngotracheal reconstruction with anterior costal cartilage grafts.

In single-stage laryngotracheal reconstruction (ss-LTR), the endotracheal tube is used as a stent. The optimal duration of stenting is not known. The stenting period requires a stay in the intensive care unit, as the patient is intubated. Sedation and, rarely, paralysis may be required. An analysis from a prospectively collected database was performed to investigate the effect of length of stenting on the outcome of ss-LTR. The outcomes used were reintubation rate and postoperative tracheostomy rate. Patients with anterior costal graft ss-LTR were selected, as they had undergone similar procedures and have similar stenosis types and grades. In 101 patients, the duration of stenting ranged from 2 to 14 days (mean, 7 days; SD, 2.6 days). No significant correlation was found between the number of days stented and the reintubation rate or the postoperative tracheostomy rate. Patients stented for longer than I week were an average of 15 months younger than those stented for less than 1 week; however, the stenosis grades for the two populations were equivalent. The differences in rates of reintubation (p = .68) and postoperative tracheostomy (p = .52) in these 2 groups were not significant. For patients undergoing ss-LTR with anterior costal cartilage grafts, no correlation was found between the number of days stented (intubated) and the reintubation rate or the postoperative tracheostomy rate.

Preventing labyrinthitis ossificans: the role of steroids.

OBJECTIVE: To identify a possible relationship between the administration of steroids at the time of diagnosis of bacterial meningitis and the development of labyrinthitis ossificans. DESIGN: Retrospective analysis of the charts of 38 children requiring cochlear implantation who presented with bacterial meningitis and then developed bilateral profound deafness. The patients' charts were reviewed for age at diagnosis, the type of antibiotic administered, and the administration, dosage, and duration of steroid (dexamethasone) therapy. Labyrinthitis ossificans was established by preoperative computed tomographic and/or magnetic resonance imaging and by the intraoperative findings as described in the operative report. PATIENTS AND METHODS: Patients were 38 children who received cochlear implantation by a single senior otolaryngologist for bacterial meningitis-related deafness. Ten patients' charts (26%) were available for full review; 9 of these 10 patients had documented pneumococcal meningitis and the other patient had Haemophilus influenzae-type meningitis. RESULTS: One of the 6 patients who received steroid therapy at the time of initial illness had documented evidence of labyrinthitis ossificans either radiographically or at the time of surgery. All 4 patients who failed to receive steroid therapy developed labyrinthitis ossificans. The results achieve statistical significance by chi2 analysis and a t test (P<.01). CONCLUSION: The results of this retrospective study are highly suggestive of a role for steroids in preventing the development of labyrinthitis ossificans in children with pneumococcal meningitis.

Surgery for pediatric subglottic stenosis: disease-specific outcomes.

To set the foundation to develop a disease-based, operation-specific model to predict the outcome of pediatric airway reconstruction surgery, we performed a retrospective database review of children operated on at a single, tertiary-care children's hospital. Over the 12-year period 1988 to 2000, a total of 1,296 airway reconstruction procedures were performed. Out of these, charts were identified for 199 children who underwent laryngotracheal reconstruction for a sole diagnosis of subglottic stenosis. Children were excluded from the study if their disorder included supraglottic, glottic, or upper tracheal disease. The main outcome measures were Myer-Cotton grade-specific decannulation and extubation rates, including both operation-specific and overall results. There were 101 children who underwent double-stage laryngotracheal reconstruction. The operation-specific decannulation rates for Myer-Cotton grades 2, 3, and 4 were 85% (18/21), 37% (23/61), and 50% (7/14) (chi2 analysis, p = .0007). The overall decannulation rates were 95% (20/21), 74% (45/61), and 86% (12/14) (chi2 analysis, p = .04). There were 98 children who underwent single-stage laryngotracheal reconstruction. The operation-specific extubation rates for Myer-Cotton grades 2, 3, and 4 were 82% (37/45), 79% (34/43), and 67% (2/3) (chi2 analysis, p = .63). The overall extubation rates were 100% (45/45), 86% (37/43), and 100% (3/3) (chi2 analysis, p = .03). Logistic regression analysis showed no effect of age (less than or greater than 2 years of age) on operation-specific or overall outcome parameters. We conclude that laryngotracheal reconstruction for pediatric subglottic stenosis remains a challenging set of procedures in which multiple operations may be required to achieve eventual extubation or decannulation. Children with Myer-Cotton grade 3 or 4 disease continue to represent a significant challenge, and refinements of techniques are being examined to address this subset of children. Disease-based, operation-specific outcome statistics are the first step in the development of a meaningful predictive model.

Methicillin-resistant Staphylococcus aureus otorrhea after tympanostomy tube placement: an emerging concern.

OBJECTIVES: To review the treatment of pediatric patients with methicillin-resistant Staphylococcus aureus (MRSA)-positive cultures as a result of otorrhea after tympanostomy tube placement in terms of both medication and isolation strategies and to highlight an emerging problem faced by the clinician with reference to treatment options as well as to the treatment of these patients in an outpatient setting. PATIENTS: Between December 1998 and January 2000, a total of 8 children between the ages of 1 and 11 years had MRSA-positive cultures as a result of otorrhea after tympanostomy tube placement. MAIN OUTCOME MEASURES: The Department of Infectious Diseases was notified, and a variety of topical antibiotic treatments were administered. Arch Otolaryngol Head Neck Surg. 2000;126:1440-1443

Pediatric fiberoptic endoscopic evaluation of swallowing.

Pediatric dysphagia is the presenting feature of many underlying diagnoses. Between July 1993 and July 1999, 643 fiberoptic endoscopic evaluations of swallowing (FEES) were performed on 568 patients. The median age of the population was 2.5 years (range, 3 days to 21 years). The principal medical and surgical diagnoses of the patients at the time of presentation to the FEES clinic were prospectively recorded: 36% of the patients presented with a diagnosis of structural abnormalities of the upper aerodigestive tract or airway; 26% with neurologic diagnoses; 12% with gastroenterological disorders; 8% with genetic syndromes; 7% with pulmonary dysfunction; 5% with prematurity; 3% with cardiovascular anomalies; and 2% with metabolic problems. The patients were classified according to the following feeding regimens: 9% normally fed; 38% orally fed with limitations; 13% orally fed, but with required supplemental tube feedings; and 40% prohibited from taking nutrition orally. The FEES enabled the following classification of feeding abnormalities: 15% had normal feeding; 56% exhibited behavioral abnormalities, including sensory-based feeding disorders; 15% exhibited structural abnormalities; 16% exhibited neurologic abnormalities; 1.5% exhibited metabolic abnormalities; and 0.5% exhibited cardiorespiratory abnormalities. The unique aspects of pediatric dysphagia are highlighted, and the role of FEES in the workup of this challenging aspect of pediatric otolaryngology is discussed.

Subglottic stenosis associated with transesophageal echocardiography.

Transesophageal echocardiography (TEE) is used extensively to assess cardiac function and anatomical relationships in both adults and children. Although considered a noninvasive procedure, TEE in infants and small children may result in airway complications. A patient who developed subglottic stenosis after the use of TEE during a cardiac procedure is reported.

Reversible sensorineural hearing loss following administration of muromonab-CD3 (OKT3) for cadaveric renal transplant immunosuppression.

This prospective study is a follow-up to a case report noting reversible sensorineural hearing loss after administration of OKT3 for immunosuppression in a steroid-resistant renal cadaveric transplant patient who was rejecting his transplant. The objective is to determine the interval estimate for incidence of sensorineural hearing loss following treatment with OKT3. Seven patients were admitted to the Renal Transplant Service at Montefiore Medical Center from July 1996 to July 1997 with steroid-resistant rejection of renal cadaveric transplants and received OKT3 as an immunosuppressant. All 7 patients received 3 audiograms: the first, prior to the administration of the first dose of OKT3, the second, 48 to 72 hours after administration of OKT3, and the third, approximately 2 weeks after administration of OKT3. Five of the 7 patients (71%) demonstrated a sensorineural hearing loss of 15 dB or greater at frequencies of 8 to 12 kHz. Four of the 5 patients with audiographic changes had near-complete to complete recovery of their high-frequency thresholds after discontinuation of the drug regimen. In conclusion, OKT3 can cause sensorineural hearing loss. This side effect is mainly reversible after 2 weeks following discontinuation of the drug. Patients receiving OKT3 should be forewarned of this possible side effect prior to the administration of OKT3.

Congenital laryngeal anomalies. Laryngeal atresia, stenosis, webs, and clefts.

Congenital laryngeal anomalies may occur as a result of defects in normal prenatal development. They are associated with a broad spectrum of symptoms and require treatment ranging from observation alone to complex open airway surgery. The treating otolaryngologist must organize a management strategy focused on timely diagnosis, ensuring a safe airway, and maximum conservation of respiratory, phonatory, and swallowing ability.

Reversible sensorineural hearing loss after renal transplant immunosuppression with OKT3 (muromonab-CD3).

Reversible and irreversible ototoxicity has been documented following the administration of various therapeutic agents. Reversible hearing loss is a known complication following the administration of quinine, salicylates and other nonsteroidal anti-inflammatory drugs, and erythromycin. We report a case of reversible hearing loss following OKT3 (murine monoclonal antibody CD3) administration. OKT3, a monoclonal antibody used as an immunosuppressant following cadaveric renal transplants, was associated with a transient sensorineural hearing loss that reversed following discontinuation of OKT3.

Neurotrophic effects of BDNF and CNTF, alone and in combination, on postnatal day 5 rat acoustic ganglion neurons.

The neuronal survival promoting ability of brain derived neurotrophic factor (BDNF), and ciliary neurotrophic factor (CNTF), individually and in combination, was evaluated in dissociated cell cultures of postnatal day 5 (P5) rat acoustic ganglia. The neuritogenic promoting effect of these same neurotrophic factors was examined in organotypic explants of P5 rat acoustic ganglia. The results showed that BDNF was maximally effective at a concentration of 10 ng/mL in promoting both survival and neuritogenesis of these postnatal auditory neurons in vitro. CNTF was maximally effective at a concentration of 0.01 ng/mL at promoting both survival and neuritogenesis in the acoustic ganglion cultures. BDNF had its strongest effect on neuronal survival while CNTF was most effective in stimulating neurite outgrowth. These two neurotrophic factors, when added together at their respective maximally effective concentrations, behave in an additive manner for promoting both survival and neuritic outgrowth by the auditory neurons.

Defective HSV-1 vector expressing BDNF in auditory ganglia elicits neurite outgrowth: model for treatment of neuron loss following cochlear degeneration.

The neurotrophins are a family of growth factors that play an important role in the development and maintenance of the nervous system. Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family that appears to participate in the maturation and function of mammalian auditory neurons. Forms of deafness due to varied injurious stimuli that are amenable to treatment with implantable prosthetic devices require the survival of these BDNF-responsive auditory neurons for effective outcome. To evaluate the feasibility of developing a gene therapy for deafness that may be used in conjunction with a prosthetic device, we constructed replication-defective herpes simplex virus (HSV) amplicon vectors that carry the human BDNF cDNA. Using these vectors, HSVbdnf and HSVbdnflac (expresses BDNF and Escherichia coli beta-galactosidase), we evaluated the expression and biological activity in established cell lines and explant cultures prepared from spiral ganglia of the murine ear. Gene transfer with HSVbdnf resulted in the efficient expression of human BDNF mRNA in murine fibroblasts. Using two BDNF-responsive cell lines, PC12trkB and MG87trkB, we demonstrate efficient secretion of biologically active BDNF. Finally, transduction of explanted spiral ganglia with HSVbdnflac elicited robust neuritic process outgrowth comparable to exogenously added BDNF. Overall, these data demonstrate that HSV vectors can efficiently transfer and express the BDNF gene in many cell types, including auditory neurons. Moreover, they suggest that similar vectors may be used to express the neurotrophin in auditory neurons in vivo and perhaps as adjunctive gene therapy for deafness.